AGING
June 6, 2007

The Yin and Yang of Alzheimer's

Recent research suggests a new way of understanding — and possibly preventing — Alzheimer's disease. It seems that an imbalance between two substances, called peptides, in the brain may be the real cause of this devastating neurological disease.

"We have found that two peptides, AB42 and AB40, must be in balance for normal function," said Chunyu Wang, lead researcher and assistant professor of biology at New York's Rensselaer Polytechnic Institute. "They are like the Yin and Yang of Chinese philosophy. When the peptides are produced in the correct proportions, the brain is healthy; but when that delicate balance is changed, pathological changes will occur in the brain and the person's memories become hazy, leading to eventual dementia."

Wang theorizes that this imbalance could be the principal cause of Alzheimer's disease. If he is right, then treating people with a form of AB40 might actually stop the disease from progressing.

His research is published in the June 2007 Journal of Molecular Biology.

Peptides are produced by the linking together of amino acids. The two peptides that Wang investigated were both Amyloid B-peptides (AB), composed of two amino acids called AB40 and AB42. These two peptides are ingredients in the senile or amyloid plaques that develop within the brains of those with Alzheimer's.

Scientists were already aware that at certain level, AB42 becomes toxic to brain cells, but the role of AB40, which is generated from the same protein as AB42, had not been appreciated.

Wang set out to determine what role AB42 played.

"We have found that the ratio of AB40 to AB42 plays a key role in AB42 aggregation," Wang said. "The current mode of thinking in Alzheimer's emphasizes the toxic role of AB42 but neglects the protective role of AB40. Combined with previous work on AB40 by many other groups, our data suggest that AB40 has an equally important, protective role in Alzheimer's. Thus AB42, the bad molecule, and AB40, the good molecule, are like Yin and Yang. The brain can only function normally when they are in balance."

"This has the potential to become a simple therapy to prevent the formation of toxic AB42 species," Wang added.
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